Phosphoinositide turnover signaling stimulated by ET-3 in endothelial cells from spontaneously hypertensive rats

Endothelin (ET) B-type receptor-mediated signal transduction after stimulation with ET-3 was examined in cultured aortic endothelial cells obtained from spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. The purpose of this study was to elucidate ET(B) receptor- mediated response in endothelial cells from hypertensive rat models. Non- isopeptide-selective displacement and affinity in these binding experiments suggest that aortic endothelial cell receptors for ET-3 correspond to ET(B) receptor subtypes. These receptors for ET-3 were similar in WKY and SHR endothelial cells. ET(B) receptor mRNA expression in cultured endothelial cells was also similar in WKY and SHR. However, the cytosolic free-Ca²⁺ level in the absence of extracellular Ca²⁺ as well as the inositol 1,4,5- trisphosphate level in response to ET-3 were greater in endothelial cells from SHR than in those from WKY. Phospholipase C and protein kinase C activities after stimulation with ET-3 were also greater in SHR than in WKY. The 6-ketoprostaglandin F(1α) production was also augmented in SHR, although nitric oxide formation and guanosine 3',5'-cyclic monophosphate production after stimulation with ET-3 were similar in WKY and SHR. We conclude that the phosphoinositide turnover signaling stimulated by ET-3 is augmented in cultured aortic endothelial cells from SHR compared with those from WKY.